We examine the first major wave of European exploration, conquest, and colonization in the Americas from 1492 to 1700, a complex series of encounters that profoundly changed European, American, and African peoples and cultures on both sides of the Atlantic. Themes include religious and cultural interactions; violence and coexistence in everyday life; constructions of race, gender, and ethnicity; slavery and other forms of labor; trans-Atlantic migration, both voluntary and forced; and European and indigenous anthropologies of the ‘other.’ Focus is on Spanish, French, and Portuguese territories in Latin America.